In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 109, No. 25 ( 2004-06-29), p. 3182-3190
Kurzfassung:
Background— Carvedilol but not metoprolol exhibits persistent binding to β-adrenergic receptors (β-ARs) even after washout in cell culture experiments. Here, we determined the significance of this phenomenon on human β-ARs in vitro and in vivo. Methods and Results— Experiments were conducted on human atrial trabeculae (n=8 to 10 per group). In the presence of metoprolol, isoproterenol potency was reduced compared with controls ( P 〈 0.001). In the presence of carvedilol, isoproterenol identified 2 distinct binding sites of high (36±6%; −8.8±0.4 log mol/L) and low affinity (−6.5±0.2 log mol/L). After β-blocker washout, isoproterenol potency returned to control values in metoprolol-treated muscles, whereas in carvedilol-treated preparations, isoproterenol potency remained decreased ( P 〈 0.001 versus control). In vivo studies were performed in 9 individuals receiving metoprolol succinate (190 mg/d) or carvedilol (50 mg/d) for 11 days in a randomized crossover design. Dobutamine stress echocardiography (5 to 40 μg · kg −1 · min −1 ) was performed before, during, and 44 hours after application of study medication. β-Blocker medication reduced heart rate, heart rate–corrected velocity of circumferential fiber shortening, and cardiac output compared with baseline ( P 〈 0.02 to 0.0001). After withdrawal of metoprolol, all parameters returned to baseline values, whereas after carvedilol, all parameters remained reduced ( P 〈 0.05 to 0.001) despite complete plasma elimination of carvedilol. Conclusions— Carvedilol but not metoprolol inhibits the catecholamine response of the human heart beyond its plasma elimination. The persistent β-blockade by carvedilol may be explained by binding of carvedilol to an allosteric site of β-ARs.
Materialart:
Online-Ressource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.0000130849.08704.24
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2004
ZDB Id:
1466401-X
